Pharmacovigilance and Drug Safety Compliance Update

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Pharmacovigilance and Drug Safety Compliance
Update

• GAP Analysis How We Get to Where We Want to Be

John P. Ford Sidley Austin LLP
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Core PV Concepts

• Risk identification, collection of information
• Risk assessment, characterization of information
• Risk mitigation, communication or other action
  based on assessment
• Address known risks, potential risks, and missing
  information

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Sources of PV Gaps

• Resources
• Government PV resources have expanded via
  increased appropriations and an increase in the
  amount and dedication of user fees for safety,
  but resources are still limited
• Private sector resources for IT and other PV
  investments are limited by reimbursement policies
  and market competition
• The science of safety and its limitations

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Sources of PV Gaps (continued)

• Authority and standards
• FDAAA expanded FDAs authority to obtain PV
  information
• FDA has explicit authority to order post approval
  studies or clinical trials to assess a known
  serious risk, assess signals of a serious risk,
  or to identify an unexpected serious risk when
  available data indicates the potential for a
  serious risk. Determination must be based on new
  information. Note that new information can come
  from a variety of sources, including sources
  other than the sponsor. FDA has authority to
  order labeling changes.
• REMS authority to require elements to assure
  safe use
• Clinical trials data bank expanded, other
  information must be submitted, much of which is
  assessed and made public
• Robust active surveillance

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Sources of PV Gaps (continued)

• Guidance and standards for improving PV will
  evolve as science of what information is most
  useful and the IT to collect it improve over time
• Priorities and policies
• Product life cycle
• limitations of premarket trials
• limitations of post market data
• PV is a greater priority than ever before, but
  improvements will take time
• PV will always be a work in progress, the
  science of safety is still evolving
• PV tensions include liability, privacy,
  transparency/publicity, patient/provider culture
• PV harmonization incomplete

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Collection of Information

• Pharmacogenetics, IT, harmonization, and other
  factors are changing what is known or knowable
  about drugs
• There can be tension between the goal of greater
  transparency and access to PV information.
  Issues of confidentiality, liability, resources,
  and other factors can affect the quality and
  uniformity of information collected
• There is no apparent consensus on how much of
  what kind of information is needed to optimize PV

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Characterization of Information

• Characterization of information is a work in
  progress, FDAAAs reports and studies reflect
  challenges in risk assessment and communication
• Decisions about how to address a safety concern
  are often a matter of judgment, about which
  reasonable persons with relevant expertise may
  disagree. (FDA Guidance, Drug Safety
  InformationFDAs Communication to the Public
• FDA focus on improving PV science, communication,
  and operations and management

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The Future of Drug Safety (IOM) and FDAAA

• The Institute of Medicines Report, The Future
  of Drug Safety, identified a number of drug
  safety issues and provided recommendations
• Many of the IOMs recommendations are reflected
  in FDAAA
• FDAAA implementation will be a key to identifying
  and filling PV gaps

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PV Gaps and FDAAA

• Office of Drug Safety is explicitly part of new
  drug review process
• Emphasis on product life cycle and recognition of
  limitations of pre-market clinical trials
  reflected in post-market authorities, resources,
  and responsibilities
• Greater allocations of resources, both
  appropriations and user fees, to drug safety
• Safety goals included in PDUFA goals
• Increase the amount and sophistication of active
  surveillance
• Public/private partnerships to make drug safety
  more effective and efficient

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PV Gaps and FDAAA (continued)

• Expand FDAs drug safety expertise
• Increase FDA research on drug safety issues and
  establish Office of Chief Scientist
• Increase advisory committee input and reduce
  committee member conflicts of interest
• Expand posting of clinical trial and other data
  used for FDA product review
• Assess and make public post market study results
• Increase FDA authority to require studies or
  trials in response to safety signals, time
  limited dispute resolution
• Research and reports on risk communication

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PV Gaps and FDAAA,Looking Ahead

• The Commissioner of Food and Drugs shall
  submit to the Congress a report on how best to
  communicate to the public the risks and benefits
  of new drugs and the role of the risk evaluation
  and mitigation strategy in assessing such risks
  and benefits (FDAAA, section 904).
• The Secretary shall report to the Congress on
  the ways in which the Secretary has used the
  active postmarket risk identification and
  analysis systemto identify specific drug safety
  signals and to better understand the outcomes
  associated with drugs marketed in the United
  States (FDAAA, section 905(c)).
• The Secretary shall improve transparency of
  information about drugsby maintaining an
  Internet Web site that (A) provides links to drug
  safety informationand (B) improves communication
  of drug safety information to patients and
  providers (FDAAA, section 915).

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PV Gaps and FDAAA,Looking Ahead (continued)

• The Advisory Committee on Risk Communication
  shall advise the Commissioner on methods to
  effectively communicate risks associated with the
  products regulated by the FDA (FDAAA, section
  917). The Advisory Committee on Risk
  Communication shall perform regular reviews and
  evaluations to facilitate the dispensing of risk
  communication information to patients and
  providers (FDAAA, section 915).
• The Secretary shall report to Congress on
  procedures and processes for addressing ongoing
  post market safety issues (FDAAA, section 921).
• The Secretary shall conduct a pilot program to
  ensure that clinical trial information is
  non-promotional and is not false or misleading.

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PV Gaps and FDAAA,Looking Ahead (continued)

• The Office of Chief Scientist shall develop
  postmarket safety performance measures that are
  as measurable and rigorous as the ones already
  developed for premarket review (FDAAA, section
  602).
• The Reagan Udall Foundation shall identify unmet
  needs in the development, manufacture, and
  evaluation of the safety and effectiveness,
  including post approval, of drugs and other
  products regulated by FDA (FDAAA, section 601).